Field of the Invention
The present invention relates generally to the field of implantable medication infusion systems, and more particularly to a method of screening potential recipients of an implantable medication infusion system including an implanted intraperitoneal catheter to select only those candidates having a high degree of resistance to catheter blockage probably due to fibrotic tissue growth.
Metabolism of glucose in the body is a particularly important chemical reaction which allows the utilization of the energy contained in food. The physiological system of the body has a sophisticated regulatory system which, when operating properly, maintains the level of blood glucose at an optimum level, thereby assuring the availability of adequate amounts of glucose when needed by the body.
This glucose regulatory system utilizes insulin to regulate blood glucose in two ways. First, the rate of glucose transport through the cell membrane of many body cell types is increased by insulin. In the absence of insulin, the rate of glucose transport through such cells is dramatically reduced to less than one-fourth the normal rate of glucose transport. However, excessively high insulin levels can greatly increase the rate of glucose transport to five times the normal rate. It is thereby apparent that insulin level has at least the capacity to adjust the rate of glucose absorption in the body by a factor of twenty.
Secondly, insulin acts as a regulatory hormone which is supplied to the liver. The secretion of insulin by the pancreas is stimulated by digestion and the accompanying higher glucose levels in the body, resulting in an increase in the amount of insulin secreted into the portal vein. While approximately half of the insulin secreted into the portal vein is distributed throughout the boy by the cardiovascular system, the rest of the insulin is immediately absorbed by the liver. In response to the surge of insulin, the liver produces large quantities of glucokinase, an enzyme enabling conversion of glucose into glycogen, which may be stored by the body. Much of the excess glucose entering the cardiovascular system as a result of digestion is thereby quickly removed to maintain relatively normal levels of glucose concentration in the blood.
When the level of glucose concentration in the blood later begins to drop below normal, the level of insulin secretion by the pancreas is reduced, and production of the hormone glucagon is begun. Glucagon enables the conversion of glycogen in the liver back into glucose by activating liver phosphorylase, an enzyme, and the result i the release of glucose into the cardiovascular system for distribution throughout the body. Once again, the body acts to maintain the concentration of glucose in the blood at a normal level.
The system which maintains a normal level of blood glucose is finely balanced, and the relationship between the pancreas and the liver can be easily upset. The most common problem is the situation when the pancreas no longer secretes adequate levels of insulin, a condition known as "diabetes mellitus." In some instances, the pancreas may completely cease the production of insulin.
In any event, the diminution or reduction in insulin production results in a rise in the concentration of glucose in the blood, which causes the osmotic pressure in extracellular fluids to rise above normal pressure. The result of this increase in osmotic pressure is typically significant cellular dehydration. The increase in the blood glucose concentration also affects the kidneys thereby causing them to act to remove excess glucose from the blood, in which process fluids are further removed from the body.
The diminution of insulin production is also accompanied by a substantial reduction in the transportation of glucose into most tissues of the body. In addition, an insulin shortage also prevents glucose from being stored i the liver as glycogen, thereby resulting in a lack of available glucose in the time of glucose need. In conditions in which there is an absence of sufficient levels of glucose, body ell metabolism becomes fat based instead of carbohydrate based. Heavy dependence on fat metabolism due to insufficient blood glucose concentration results in a substantial rise in the concentration of acetoacetic acid and other keto acids to as much as thirty times normal levels, thereby causing a significant reduction in the pH of blood below its normal pH level of 7.4.
When the kidneys attempt to alleviate the concentration of the various keto acids in the blood, substantial amounts of sodium are also removed, thereby further lowering the blood pH. Should the blood pH fall below 7.0, a coma state will typically be experienced, with the results frequently being fatal.
Diabetic treatment has centered on restoring proper carbohydrate metabolism by the administration of insulin. For years insulin has been administered by multiple daily injections into the peripheral circulation, either by intramuscular or subcutaneous injection, or shot, using a syringe and needle to delivers the insulin dosage to the patient at intervals up to four times a day.
As an alternative to periodic injections, the relatively recent addition of small, portable insulin infusion pumps has come as a welcome improvement. Insulin infusion pumps are utilized to administer insulin to a subcutaneous injection location in a patient in small, metered doses in an essentially continuous manner. Infusion pump therapy may be electronically controlled to deliver precise, metered doses at exactly determined intervals, thereby providing a beneficial gradual infusion of medication to the patient. In this manner, the insulin infusion pump is able to mimic the natural process by delivering both a basal rate of insulin delivery and boluses of insulin whereby overall delivery of insulin is maintained more precisely.
However, peripheral insulin administration to a subcutaneous location results in only about ten percent of the insulin administered reaching the liver, as compared to the fifty percent or so in normal individuals. Therefore, rather than hepatic glucose production being lowered first, blood glucose level is reduced due to the presence of higher than normal levels of insulin in the peripheral circulation by an increased utilization of glucose by body tissues. It is more difficult to maintain a normal level of blood glucose by using insulin injection or subcutaneous insulin infusion, since, unlike the natural feedback system of the body, hepatic glucose production is not substantially decreased by insulin which is injected or infused peripherally.
It is therefore apparent that it is desirable to administer insulin to a patient in a manner whereby a greater percentage of the insulin reaches the liver than in peripheral administration of insulin. An implantable infusion pump connected to a catheter which would deliver insulin internally rather than peripherally may be used to accomplish this objective, but since the pump and catheter ar internally implanted, they have to be capable of continuing to function effectively over an extended period of time.
Such an implantable insulin pump is disclosed in U.S. Pat. No. 4,373,527, to Fischell, in U.S. Pat. No. 4,573,994, to Fischell et al., in U.S. Pat. No. 4,525,165 to Fischell, an in U.S. Pat. No. 4,731,051, to Fischell.
The problem with implantable catheters is that they rapidly tend to become overgrown with fibrotic tissue which will close off the catheter in short order. This is particularly true in those cases where only a small flow of medication is being delivered through the catheter. Several types of catheters have been used, with the most common being a simple tube having an aperture therethrough. At the end of the tube, the aperture allows medication to exit the tube and enter the body. It will be appreciated that such an arrangement is susceptible to being covered with fibrotic tissue relatively rapidly, since the fibrotic tissue will grow around the end of the tube.
Variations include the addition of a disk which is mounted at the end of the catheter with the tube leading orthogonally to the disk with medication exiting the aperture of the tube at the center of the disk. While this design is somewhat less susceptible to clogging by the rapid growth of fibrotic tissue, in time the entire disk will be covered and the opening will be closed by parietal or fibrotic tissue. The other approach that has been used is to make the opening of a small diameter to cause the fluid to exit the catheter with a relatively high velocity.
Another approach to an implantable catheter is illustrated in U.S. patent application Ser. No. 043,796, filed on Apr. 29, 1987, to Diaz et al. This application is assigned to the assignee of the present application, and is hereby incorporated herein by reference. With the catheter of the Diaz et al. invention, an implantable catheter having a novel catheter terminator configuration having a recessed area which inhibits the ability of fibrotic tissue to choke off fluid delivered through the catheter is implanted in the tissue of the momentum. The distal or delivery end is placed into a fold in the momentum tissue, which is then sutured around the delivery end of the catheter.
Placement of he Diaz et al. catheter causes the insulin to be absorbed effectively in a manner mimicking to the greatest extent possible the body's utilization of insulin. The terminator of the catheter is held in a secure location, with predictable absorption of the insulin. In addition, fibrotic tissue growth may happen at a somewhat reduced pace from other locations in the body, and occlusion of the aperture is prevented by the fact that the recessed area is spaced away from the place where fibrotic tissue will grow.
It will be appreciated that the placement and the configuration of even the Diaz et al. implantable catheter leaves something to be desired. Since the implantation of a catheter generally involves major surgery, it is desirable that an implantable catheter be capable of operating over an extended period of time without requiring repair or replacement. It seems that the obstruction of any catheter design will occur over a period of time in the body due to the body's natural defense mechanism.
It is the primary objective of the present invention to provide a means of selection for those patients considered for receipt of an implanted pump and catheter who will have an enhanced likelihood of extended catheter longevity. As such, it is an objective to provide selection criteria which will optimize, to the extent possible, the probability that an implanted catheter will continue to function effectively to deliver insulin or other therapeutic medication for an extended period of time.
The criteria will accordingly reduce the likelihood of subsequent surgery to repair or replace an obstructed catheter, and as such represent substantial advantage in the selection of appropriate patients to whom the benefits of implantation far outweigh the possible risks. It may therefore be perceived that the advantages of the method comprising the present invention will enhance to the maximum degree possible that a patient in whom a catheter is implanted will not require surgery to repair or replace the catheter for an extended period of time. This makes the method of the present invention a highly desirable enhancement to implantable medication infusion system therapy.